This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Cells of the developing mammalian brain respond to a complex array of extracellular stimuli ultimately fashioning an intricate and powerful tissue. However, misinterpretation of developmental neuronal stimuli can lead to devastating human brain disorders. Phosphorylation is one of the most dynamic regulators of protein function initiated by an extracellular signal. Acquiring an understanding of the phosphoregulatory mechanisms of only one neuronal stimulus has traditionally been highly labor intensive. In addition, traditional approaches have largely required a prior knowledge of, as well as biochemical reagents for, putative pathway components. Mass spectrometry (MS)-based proteomics has emerged as an invaluable technology to study protein phosphorylation and is now poised for systems scale quantitative phosphoproteomic analyses in a largely unbiased manner. By taking an interdisciplinary approach merging biochemistry, MS-based proteomics and developmental biology I aim to map essential phosphoregulatory pathways governing mammalian brain development with the focus of this proposal on the critical Reelin Signaling pathway.